This proposal outlines a three-year research career development program that will enable the principal investigator to further develop a research career after a period in administration. The PI is a chemical engineering faculty member with biomedical research interests who will benefit from an expansion of research skills and adeptness in this area. A multi-faceted research project on sickle cell adhesion forms the core of the program that brings together eminent experts who will work closely with the PI. Mentor, David Golan, M.D., Ph.D. of Harvard Medical School (HMS) is an expert in bipophysical and imaging techniques, red cell membranes, and sickle cell disease, and has trained over twenty physicians and researchers. Collaborator, D. K. Kaul, Ph.D. of Albert Einstein College of Medicine (AECM) is an expert in sickle cell investigations involving ex vivo animal models, and collaborator, Ulrich von Andrian, M.D., Ph.D. of Harvard Medical School is an expert in studies using intravital microscopy models. It is widely understood that the pathophysiology of vaso-occlusion in sickle cell disease is complex and muti-factorial, and that its treatment will require therapeutic approaches that address mutiple factors. The abnormal adhesion of sickle red blood cells to the vascular endothelium may participate in the initiation of vaso-occlusion, and may occur by multiple mechanisms. The proposed project will apply a muti-pronged approach to the investigation of sickle cell adhesion mechanisms and potential therapeutic agents. We will use state-of-the-art biophysical tools to quantify the basis for sickle cell adhesion at the level of individual adhesion molecules and predict the strength of adhesion. The predictions will be tested in complementary model systems. Experiments will be carried out in the laboratories of the PI and those of the mentor and collaborators. The outstanding research environments of the Department of Biological Chemistry and Molecular Pharmacology, HMS (Golan), The Department of Medicine, AECOM (Kaul), and the Center for Blood Research, HMS (von Andrian) provide an excellent setting for the PI to gain the expertise and research skills that will allow maximal career development.